Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease

BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.

Hypersonic sliding target tracking in near space

To improve the tracking accuracy of hypersonic sliding target in near space,the influence of target hypersonic movement on radar detection and tracking is analyzed,and an IMM tracking algorithm is proposed based on radial velocity compensating and cancellation processing of high dynamic biases under the earth centered earth fixed(ECEF) coordinate.Based on the analysis of effect of target hypersonic movement,a measurement model is constructed to reduce the filter divergence which is caused by the model mismatch.The high dynamic biases due to the target hypersonic movement are approximately compensated through radial velocity estimation to achieve the hypersonic target tracking at low systematic biases in near space.The high dynamic biases are further eliminated by the cancellation processing of different radars,in which the track association problem can be solved when the dynamic biases are low.An IMM algorithm based on constant acceleration(CA),constant turning(CT) and Singer models is used to achieve the hypersonic sliding target tracking in near space.Simulation results show that the target tracking in near space can be achieved more effectively by using the proposed algorithm.